Single-molecule microscopy on model membranes reveals anomalous diffusion

Biophys J. 1997 Aug;73(2):1073-80. doi: 10.1016/S0006-3495(97)78139-6.

Abstract

The lateral mobility of lipids in phospholipid membranes has attracted numerous experimental and theoretical studies, inspired by the model of Singer and Nicholson (1972. Science, 175:720-731) and the theoretical description by Saffman and Delbrück (1975. Proc. Natl. Acad. Sci. USA. 72:3111-3113). Fluorescence recovery after photobleaching (FRAP) is used as the standard experimental technique for the study of lateral mobility, yielding an ensemble-averaged diffusion constant. Single-particle tracking (SPT) and the recently developed single-molecule imaging techniques now give access to data on individual displacements of molecules, which can be used for characterization of the mobility in a membrane. Here we present a new type of analysis for tracking data by making use of the probability distribution of square displacements. The potential of this new type of analysis is shown for single-molecule imaging, which was employed to follow the motion of individual fluorescence-labeled lipids in two systems: a fluid-supported phospholipid membrane and a solid polymerstabilized phospholipid monolayer. In the fluid membrane, a high-mobility component characterized by a diffusion constant of 4.4 microns2/s and a low-mobility component characterized by a diffusion constant of 0.07 micron2/s were identified. It is proposed that the latter characterizes the so-called immobile fraction often found in FRAP experiments. In the polymer-stabilized system, diffusion restricted to corrals of 140 nm was directly visualized. Both examples show the potentials of such detailed analysis in combination with single-molecule techniques: with minimal interference with the native structure, inhomogeneities of membrane mobility can be resolved with a spatial resolution of 100 nm, well below the diffraction limit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diffusion
  • Dimyristoylphosphatidylcholine / chemistry*
  • Fluorescent Dyes
  • Kinetics
  • Lipid Bilayers / chemistry*
  • Liposomes / chemistry*
  • Microscopy, Fluorescence / methods
  • Models, Chemical
  • Molecular Conformation
  • Phosphatidylcholines / chemistry*
  • Phosphatidylethanolamines / chemistry*
  • Rhodamines / chemistry*
  • Sensitivity and Specificity

Substances

  • Fluorescent Dyes
  • Lipid Bilayers
  • Liposomes
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Rhodamines
  • triethylammonium N-(6-tetramethylrhodaminethiocarbamoyl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine
  • tetramethylrhodamine isothiocyanate
  • 1-palmitoyl-2-oleoylphosphatidylcholine
  • Dimyristoylphosphatidylcholine